Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypogammaglobulinemia during adulthood can lead to recurrent infectious diseases, particularly pneumonia, otitis, and sinusitis, mainly due to Streptococcus pneumoniae and Haemophilus influenzae. Physicians must discriminate between primary and secondary hypogammaglobulinemia to provide appropriate treatment. Common variable immunodeficiency (CVID) is the most common cause of primary hypogammaglobulinemia diagnosed in adulthood. Clinical features include various combinations of infectious diseases, autoimmune diseases, lymphoproliferative disorders, and gastrointestinal diseases. Mutations in genes responsible for primary hypogammaglobulinemia in children are occasionally described in adults with CVID. ICOS and TACI deficiencies have recently been reported in a few CVID patients, although most cases have no proven genetic defects. The DefI cohort is recruiting adults with CVID throughout France. It will make it possible to describe the clinical, immunological, and genetic features of French patients with hypogammaglobulinemia and will help us to understand this immune deficiency better.
 ...
PMID:[Adult-onset primary hypogammaglobulinemia]. 1671 Jan 62

TNFRSF13B/TACI defects have been associated with CVID pathogenesis and/or phenotype, especially the development of benign lymphoproliferation and autoimmunity. Our purpose was to investigate the role of TNFRSF13B/TACI defects in the pathogenesis of two common lymphoproliferative disorders, namely, sarcoidosis and tonsillar hypertrophy (TH). 105 patients (71 with sarcoidosis and 34 with TH, including 19 without infectious causative and 15 due to Haemophilus influenzae) were analyzed for TNFRSF13B/TACI defects. Two out of 19 TH patients without infectious cause (10.5%) and 2 patients with sarcoidosis (2.8%) displayed rare TNFRSF13B/TACI defects (I87N, L69TfsX12, E36L, and R202H, resp.). Both mutations identified in TH patients have been assessed as deleterious for protein function, while the patient with the R202H mutation and sarcoidosis exhibited also sIgG4D. Our study further supports the notion that TNFRSF13B/TACI defects alone do not result in CVID but may be also found frequently in distinct clinical phenotypes, including benign lymphoproliferation and IgG subclass deficiencies.
...
PMID:Heterozygous alterations of TNFRSF13B/TACI in tonsillar hypertrophy and sarcoidosis. 2395 60

The respiratory tract pathogen Haemophilus influenzae frequently causes infections in humans. In parallel with all Gram-negative bacteria, H. influenzae has the capacity to release OMV. The production of these nanoparticles is an intriguing and partly unexplored phenomenon in pathogenesis. Here, we investigated how purified human peripheral blood B lymphocytes respond to OMV derived from unencapsulated, i.e., NTHi and the nonpathogenic Haemophilus parainfluenzae. We found that H. influenzae OMV directly interacted with the IgD BCR, as revealed by anti-IgD pAb and flow cytometry. Importantly, H. influenzae OMV-induced cellular activation via IgD BCR cross-linking and TLR9 resulted in a significant proliferative response. OMV isolated from the related species H. parainfluenzae did not, however, interact with B cells excluding that the effect by H. influenzae OMV was linked to common membrane components, such as the LOS. We also observed an up-regulation of the cell surface molecules CD69 and CD86, and an increased IgM and IgG secretion by B cells incubated with H. influenzae OMV. The Igs produced did not recognize H. influenzae, suggesting a polyclonal B cell activation. Interestingly, the density of the cell surface receptor TACI was increased in the presence of OMV that sensitized further the B cells to BAFF, resulting in an enhanced IgG class-switch. In conclusion, the ability of NTHi OMV to activate B cells in a T cell-independent manner may divert the adaptive humoral immune response that consequently promotes bacterial survival within the human host.
...
PMID:Diversion of the host humoral response: a novel virulence mechanism of Haemophilus influenzae mediated via outer membrane vesicles. 2455 May 22